Hagelstein J, Kist A, Stremmel W, Galle P R
Department of Internal Medicine IV, University Hospital Heidelberg, Germany.
Arzneimittelforschung. 1998 Mar;48(3):343-7.
Interferon-alpha (IFN-alpha) and other cytokines are able to interfere with hepatitis B virus (HBV) replication. However, a sustained antiviral effect is achieved only in 25% to 40% of the patients with chronic HBV infection and clearance of the virus rarely occurs, stressing the need for developing therapeutic alternatives. In this study the antiviral potential of a new recombinant interferon, IFN-omega was investigated. IFN-omega was assessed in comparison with IFN-alpha 2c, IFN-gamma, and TNF-alpha with respect to production of HBV proteins and DNA in HepG2.2.15 cells, a HBV-DNA transfected hepatoma cell line which produces infectious viral particles. Cells were seeded at different states of confluence (20%-90%) and treated with increasing concentrations of interferons (5 to 5,000 U/ml), TNF-alpha (5 to 500 ng/ml), or combinations of both for one to three days. IFN-omega reduced the production of HBsAg down to 59% of the untreated controls, which was comparable to the reduction obtained by treatment with IFN-alpha (60%), the standard interferon used for the treatment of chronic HBV infections. The strongest inhibition, however, was achieved by treatment with 500 ng/ml TNF-alpha (42%). Likewise, production of HBeAg and synthesis of HBV DNA were inhibited to similar degrees by the different interferons. In non-replicating high-density cultures only TNF-alpha was effective. IFN-omega is of similar antiviral potential as IFN-alpha in this in vitro experimental system.
α干扰素(IFN-α)和其他细胞因子能够干扰乙型肝炎病毒(HBV)的复制。然而,只有25%至40%的慢性HBV感染患者能够实现持续的抗病毒效果,病毒清除的情况很少发生,这凸显了开发其他治疗方法的必要性。在本研究中,对一种新型重组干扰素ω干扰素(IFN-ω)的抗病毒潜力进行了研究。在HBV-DNA转染的肝癌细胞系HepG2.2.15细胞中,就HBV蛋白和DNA的产生而言,将IFN-ω与IFN-α 2c、IFN-γ和TNF-α进行了比较,该细胞系可产生传染性病毒颗粒。将细胞以不同的汇合状态(20% - 90%)接种,并用递增浓度的干扰素(5至5000 U/ml)、TNF-α(5至500 ng/ml)或两者的组合处理1至3天。IFN-ω将HBsAg的产生降低至未处理对照的59%,这与用IFN-α(60%)(用于治疗慢性HBV感染的标准干扰素)处理所获得的降低程度相当。然而,用500 ng/ml TNF-α处理可实现最强的抑制作用(42%)。同样,不同的干扰素对HBeAg的产生和HBV DNA的合成也有相似程度的抑制作用。在非复制性高密度培养中,只有TNF-α有效。在这个体外实验系统中,IFN-ω具有与IFN-α相似的抗病毒潜力。